Clinical pharmacology

Oral etoposide capsules have bioavailability of 60% with extensive variation. Etoposide absorption appears to be non-linear with decreased bioavailability at doses above 200 mg. Etoposide phosphate has a similar degree of bioavailability and suggestions of non-linear absorption.

Both etoposide and teniposide are heavily protein-bound; use in patients with low albumin concentrations will result in greater than expected systemic toxicity due to the larger free (unbound) drug concentrations. Although both etoposide and teniposide are distributed into the CSF, they achieve concentrations of 0.1-4% of that measured simultaneously in plasma.

Both etoposide and teniposide are extensively metabolized. Production of a catechol metabolite is mediated through P450 3A4 and may have intrinsic cytotoxic activity. Etoposide glucuronide has been found to account for up to 30% of the administered dose. Etoposide is more rapidly eliminated than teniposide with:

♦ Faster systemic clearance

♦ Greater renal clearance

♦ Shorter elimination half-life

Linear relationships between etoposide systemic clearance and creatinine clearance have been described for both adult and paediatric patients. Both etoposide and teniposide have demonstrated pharma-codynamic relationships, where measures of systemic exposure (AUC, Css, trough concentrations, etc.) are correlated with haematological toxicity.

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